METABOLIC BALANCES OF SULFUR IN PATIENTS WITH
HEPATOLENTICULAR DEGENERATION AND EFFECT OF THE
USE OF D-PENICILLAMINE
HORACIO M . CANELAS*;
FRANCISCO B . D E JORGE**; WALDIR A . T O G N O L A * * *
Though a great deal of knowledge has been achieved in regard to the
metabolic disorders of Wilson's disease, many problems are still unsolved
The metabolic balances of sulfur in two cases of hepatolenticular
de-generation submitted to mixed and vegetarian diets
1have been studied
The effect of D-penicillamine on the balance was also analyzed.
M A T E R I A L A N D M E T H O D S
C A S E 1: V . M . , a 22-year-old w o m a n w h o s e s y m p t o m s had started a year
earlier; the neurological e x a m i n a t i o n showed the characteristic facies, bilateral Kayser-Fleischer corneal rings, a severe w i n g - b e a t i n g t r e m o r in the upper limbs, unsteady gait, slurred speech, and m i l d rigidity of the upper limbs. T h e m e a n blood serum copper content w a s 2 9 ¿¿g/lOO m l , ceruloplasmin level 3 m g / 1 0 0 m l ( H o u c h i n m e t h o d ) , aminoaciduria 4 3 7 m g / 2 4 hr. T h e liver biopsy showed a post-necrotic cirrhosis.
C A S E 2 : J . C . M . , a 27-year-old m a n whose disease started t w o years before
w i t h m e n t a l disorder and a severe tremor in the upper limbs. T h e r e were bilateral Kayser-Fleischer rings b u t m u s c l e tone, gait, and speech were n o r m a l . T h e m e a n blood serum copper w a s 4 5 / i g / 1 0 0 m l , ceruloplasmin 0 m g / 1 0 0 m l , aminoaciduria 410 m g / 2 4 hr. T h e liver biopsy showed f a t t y infiltration.
The patients were submitted to a v e g e t a r i a n diet containing 9 0 0 m g of sulfur and to a m i x e d diet containing 1,350 m g .
Case 1 w a s k e p t in metabolic b a l a n c e for 42 days, including 2 0 days on v e g e -tarian diet, 1 3 days on m i x e d diet, a n d 9 days o n v e g e t a r i a n diet a g a i n p l u s 2,000 m g of D-penicillamine (this daily dosis contains 4 3 0 m g of t o t a l sulfur, w h i c h were computed in t h e b a l a n c e ) . C a s e 2 w a s k e p t in m e t a b o l i c balance for 34 days, including 1 2 days on v e g e t a r i o n diet, 1 3 days on m i x e d diet, and 9 days on v e g e t a r i a n diet p l u s 2,000 m g of D-penicillamine. E a c h balance w a s divided in periods f r o m 3 to 6 days.
A t the end of each period feces and a l i m e n t a r y residues, which w e r e collected in glass containers kept in a refrigerator, w e r e weighed, m i x e d and h o m o g e n i z e d in a W h a r i n g Bendor. D u p l i c a t e s a m p l e s of e a c h m a t e r i a l w e r e then s u b m i t t e d t o t h e a n a l y t i c a l m e t h o d . T h e ingesta w e r e t h e difference b e t w e e n the k n o w n sulfur c o n t e n t of each type of diet and the concentration in the a l i m e n t a r y residues. Urine w a s collected daily under the s a m e conditions as feces, and the 2 4 - h o u r v o l u m e determined.
T o t a l sulfur w a s determined by the turbidimetric m e t h o d ( D e Jorge et a l .4 ) which w a s detailed for m e t a b o l i c b a l a n c e studies elsewhere ( C a n e l a s e t a l .2
) .
R E S U L T S T h e results are s u m m a r i z e d in T a b l e s 1 and 2 .
C O M M E N T S
A positive sulfur balance was evidenced in both patients, particularly
in J . C M . under mixed diet, who showed then an average daily sulfur
balance of + 6 2 mg ± 14.1, significantly higher (i = 5.676, P < 0.001)
than the normal mean (23.2 mg ± 17.3) reported by De Jorge and Cintra
3.
The administration of D-penicillamine induced a markedly negative
ba-lance, mostly through the promotion of a progressive increase of the urinary
excretion.
In the blood serum the inorganic sulfur contents were always within
normal limits (De Jorge et a l .
5) except when the patients were submitted
to D-penicillamine therapy, in which case the levels showed a progressive
rise.
S U M M A R Y
The metabolic balances of sulfur in two cases of hepatolenticular
degeneration were studied. A positive balance was found in both cases; in
one patient submitted to mixed diet, the average was significantly higher
than the normal mean.
The administration of D-penicillamine promoted a marked increase in
the urinary excretion of sulfur, leading to a strongly negative balance.
The blood sulfur contents, which were normal in the control periods,
showed a progressive increment after D-penicillamine was started.
R E S U M O
Balanços metabólicos do enxôfre em pacientes com degeneração
hepatolenticular e efeito da administração de D-penicilamina
A administração de D-penicilamina promoveu acentuado aumento da
excreção urinária do enxôfre, levando a um balanço fortemente negativo.
As concentrações de enxôfre no soro sangüíneo, que eram normais no
período de contrôle, sofreram progressivo incremento após a instituição do
tratamento com D-penicilamina.
R E F E R E N C E S
1 . C A N E L A S , H . M . ; D e J O R G E , F . B . & T O G N O L A , W . A . — M e t a b o l i c b a l a n c e s o f c o p p e r i n p a t i e n t s w i t h h e p a t o l e n t i c u l a r d e g e n e r a t i o n s u b m i t t e d t o v e g e t a r i a n a n d m i x e d d i e t s . J. N e u r o l . N e u r o s u r g . P s y c h i a t . 3 0 : 3 7 1 , 1 9 6 7 .
2 . C A N E L A S , H . M . ; D e J O R G E , F . B . & T O G N O L A , W . A . — M e t a b o l i c b a l a n c e s o f s u l f u r in p a t i e n t s w i t h m e t a c h r o m a t i c l e u c o d y s t r o p h y . A r q . N e u r o - P s i q u i a t . ( S ã o P a u l o ) 2 6 : 3 2 5 , 1 9 6 8 .
3 . D e J O R G E , F . B . & C I N T R A , A . B . U . — M e t a b o l i s m o d o e n x ô f r e . B a l a n ç o s m e t a b ó l i c o s e m a d u l t o s n o r m a i s s o b d i e t a g e r a l e s o b d i e t a e x c l u s i v a m e n t e v e g e t a l . R e v . p a u l . M e d . 6 9 : 2 5 . 1 9 6 6 .
4 . D e J O R G E , F . B . ; S I L V A , A . G . & C I N T R A , A . B . U . — D e t e r m i n a ç ã o q u a n t i t a t i v a d o e n x ô f r e n o s m a t e r i a i s b i o l ó g i c o s . R e v . b r a s . M e d . 2 1 : 4 9 1 , 1 9 6 4 . 5 . D e J O R G E , F . B . ; C A N E L A S , H . M . & Z A N I N I , A . C . — M e t a b o l i s m o d o e n x ô f r e . V a l o r e s n o r m a i s n o s o r o s a n g ü í n e o , l í q u i d o c e f a l o r r a q u e a n o , s a l i v a , u r i n a e f e z e s . R e v . p a u l . M e d . 6 5 : 3 3 2 , 1 9 6 4 .
Departamento de Neurologia — Faculdade de Medicina da Universidade de São Paulo
